August 2013

August 05, 2013

In today’s
new edition of JCB, Faurobert et al. reveal
that the CCM complex – a group of proteins associated with cerebral cavernous
malformations – regulate the interactions between vascular endothelial cells
and the extracellular matrix. By stabilizing an inhibitor of β1 integrin called
ICAP-1, the CCM complex limits β1 integrin-based adhesion and cell
contractility. As the authors explain in this week’s In Focus, in the absence
of CCM proteins, β1 integrin activation initiates a positive feedback
loop that disrupts intercellular adhesions, thereby compromising vascular
integrity.

Meanwhile,
Dix et al. describe how a protein associated with the neurodevelopmental
disorder lissencephaly promotes the assembly of dynein motor complexes on mRNA
cargoes. Lis1 associates with localization signals in certain mRNAs, and, by
recruiting the dynein motor and its accessory complex dynactin, it helps
transport these RNAs to the apical cytoplasm of Drosophila embryos. You can learn how this relates to Lis1’s role
in other dynein-dependent transport processes in this summary.

Allison
et al. reveal how a protein linked to hereditary spastic paraplegia promotes
the traffic of endosomal tubules that recycle proteins back to the cell
surface. Spastin is a microtubule-severing protein and this activity is required
to pinch off membrane tubules from sorting endosomes. In the absence of spastin
or its binding partner, the ESCRT-III component IST-1, membrane receptors are degraded instead of being returned to the cell surface. Senior author
Evan Reid explains how this might cause neurodevelopmental problems here.

Vidal-Eychenié
et al. describe how two protein kinases team up to respond to DNA damage at
stalled replication forks in cancer cells. Stalled replication forks collapse
to generate DNA double strand breaks and stretches of single stranded DNA, lesions signaled by the kinases DNA-PKcs and ATR, respectively. Vidal-Eychenié
et al. show that the two kinases synergize with each other at collapsed forks
to enhance the DNA damage response and reduce genome instability. Because this
type of damage is common in cancer cells, senior author Angelos Constantinou
explains here that inhibiting this pathway could be a way to selectively target
tumor cells in vivo.

And
finally for today, I’ll point you in the direction of this month’s biosights
video podcast, in which Antonio Jacinto describes how epithelial wound repair begins with a wave of
actomyosin assembly and cell constriction that flows through cells toward the
wound edge to promote assembly of the actomyosin “purse-string” that draws the
wound closed. You can watch below or subscribe in iTunes. And if you’d like to
discuss this paper in your next Journal Club, why not download our Journal Club
Pack to aid your discussion?

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